Investigating iPSC-Derived Macrophage Stimulation with Oxidised Low-Density Lipoprotein as an Effective In Vitro Model of Foam Cells in Atherosclerosis
type: CreativeWork
description: One of the earliest changes found in vessel walls at predilection sites for atherosclerotic plaque formation involves the retention and modification of lipoprotein particles. Macrophages and vascular smooth muscle cells (VSMCs) in the arterial wall respond by ingesting large quantities of the modified lipoproteins, such as oxidised low-density lipoproteins (oxLDLs), which are then metabolised to release cholesterol and cholesterol esters for use or recycling. Chronic uptake of modified particles eventually reduces the ability of macrophages and VSMCs to effectively break down and release the lipoprotein metabolites, causing intracellular accumulation of lipids. Existing studies have described potential foam cell-like populations using single cell RNA sequencing (scRNA-seq) of plaques, however due to known limitations of whole cell and more recent findings expanding our current knowledge of foam cell biology, much remains to be explored. Foam cells can be generated in vitro by lipid loading with modified lipoproteins or cholesterol, however, with a growing appreciation for the complexity of foam cells in vivo there remains uncertainty in which aspects of foam cell formation can be recapitulated with such models. To overcome some of the known drawbacks of single cell isolation, single nuclei extraction was optimised and applied to the selected vascular samples. One novel single nuclei and two existing single cell plaque RNA-seq datasets were analysed, showing successful annotation of expected plaque cell types and identification of individual foam cell populations, which demonstrated that single nuclei sequencing can be applied to vascular samples to describe their cellular heterogeneity. Intriguingly, a population of potential VSMC-derived foam cells could be seen to localise with macrophages when visualising cell populations in the single nuclei dataset, which had not been observed in existing single cell datasets. To identify foam cells in early stages of plaque de…
abstract: One of the earliest changes found in vessel walls at predilection sites for atherosclerotic plaque formation involves the retention and modification of lipoprotein particles. Macrophages and vascular smooth muscle cells (VSMCs) in the arterial wall respond by ingesting large quantities of the modified lipoproteins, such as oxidised low-density lipoproteins (oxLDLs), which are then metabolised to release cholesterol and cholesterol esters for use or recycling. Chronic uptake of modified particles eventually reduces the ability of macrophages and VSMCs to effectively break down and release the lipoprotein metabolites, causing intracellular accumulation of lipids. Existing studies have described potential foam cell-like populations using single cell RNA sequencing (scRNA-seq) of plaques, however due to known limitations of whole cell and more recent findings expanding our current knowledge of foam cell biology, much remains to be explored. Foam cells can be generated in vitro by lipid loading with modified lipoproteins or cholesterol, however, with a growing appreciation for the complexity of foam cells in vivo there remains uncertainty in which aspects of foam cell formation can be recapitulated with such models. To overcome some of the known drawbacks of single cell isolation, single nuclei extraction was optimised and applied to the selected vascular samples. One novel single nuclei and two existing single cell plaque RNA-seq datasets were analysed, showing successful annotation of expected plaque cell types and identification of individual foam cell populations, which demonstrated that single nuclei sequencing can be applied to vascular samples to describe their cellular heterogeneity. Intriguingly, a population of potential VSMC-derived foam cells could be seen to localise with macrophages when visualising cell populations in the single nuclei dataset, which had not been observed in existing single cell datasets. To identify foam cells in early stages of plaque de…
author: Imaz, Maria
language: eng
keywords: atherosclerosis, bulk RNA sequencing, cardiovascular biology, foam cell, histology, induced pluripotent stem cell, ips, ipsc, low density lipoprotein, macrophage, single nuclei, single nuclei RNA sequencing, transcriptomics
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/41b6e38b-843b-4656-9423-7cefcf79e5f6/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2023-09-29
date modified: 2026-07-22T22:24:27Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.109947